Oral TP-3654 for Myelofibrosis

Recruiting at 82 trial locations

Overseen By Jordan Simpson

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sumitomo Dainippon Pharma Oncology, Inc

Must be taking: Ruxolitinib, Momelotinib

Must not be taking: Systemic steroids

Disqualifiers: Chronic liver disease, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 12

Duration: 24 weeks

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, TP-3654, for individuals with myelofibrosis, a type of blood cancer. The study aims to assess the safety and effectiveness of TP-3654, both alone and in combination with other treatments like ruxolitinib or momelotinib. It is open to those with intermediate or high-risk myelofibrosis who have experienced issues with their current JAK inhibitor treatment or cannot continue with it. Participants must have conditions such as an enlarged spleen and specific symptoms related to myelofibrosis. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial does not specify that you must stop all current medications, but certain treatments like systemic antineoplastic therapy or experimental therapies must be stopped at least 2 weeks or 5 half-lives before starting the trial. If you are on a JAK inhibitor like ruxolitinib, you may need to taper off over at least 1 week. Hydroxyurea or anagrelide can be taken up to 24 hours before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TP-3654, also known as nuvisertib, is under investigation for its safety and effectiveness in treating myelofibrosis, a type of bone marrow cancer. Early results suggest that TP-3654 is generally well-tolerated by patients. In studies, patients taking TP-3654 alone or with other medications like ruxolitinib or momelotinib did not experience serious side effects that would prevent dose escalation.

When combined with ruxolitinib, studies in mice showed promising improvements, and human trials are now assessing if similar results occur. Early findings also suggest that using TP-3654 with momelotinib is well-tolerated and effective against myelofibrosis.

Overall, the ongoing Phase 1/2 trials aim to confirm these early findings and better understand the treatment's safety and mechanism of action. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for myelofibrosis, which often include JAK inhibitors like ruxolitinib and momelotinib, TP-3654 offers a fresh approach by targeting different pathways. TP-3654 is a selective PIM kinase inhibitor, which means it can potentially reduce inflammation and fibrosis in a novel way. Researchers are excited because this could mean improved symptoms and possibly fewer side effects compared to existing options. Additionally, TP-3654 can be used alone or in combination with standard therapies, potentially enhancing their effectiveness. This versatility and new mechanism of action are what make TP-3654 stand out in the treatment landscape for myelofibrosis.

What evidence suggests that this trial's treatments could be effective for myelofibrosis?

Research has shown that TP-3654 holds promise for treating myelofibrosis. In this trial, participants in Arm 1 will receive TP-3654 alone. Specifically, 22.2% experienced a significant decrease in spleen size, and many reported fewer symptoms. Participants in Arm 2 will receive TP-3654 combined with ruxolitinib, which studies have shown helps normalize blood cell counts and further reduce spleen size. Meanwhile, Arm 3 will explore TP-3654 in combination with momelotinib, where early data suggests lasting symptom relief and improved blood health. These findings highlight TP-3654's potential to manage symptoms and enhance the quality of life for people with myelofibrosis. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with primary or secondary myelofibrosis, a type of bone marrow cancer. They must have tried and failed JAK inhibitor treatment or be ineligible for it. Participants need to have certain blood counts, organ function within specific limits, and a life expectancy of at least 3 months. They can't join if they've had recent surgeries or other treatments that could interfere with the study.

Inclusion Criteria

I agree to give bone marrow samples at the start and every 6 months during the study.

My spleen is enlarged, confirmed by a doctor's exam or imaging tests.

- Life expectancy ≥ 3 months

Exclusion Criteria

My electrolyte levels are stable or can be corrected.

I haven't had cancer treatment or experimental therapy in the last 14 days or 5 half-lives, whichever is longer.

I have had my spleen removed or received spleen radiation in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nuvisertib (TP-3654) in various combinations depending on the arm, with dose-escalation to assess safety, tolerability, pharmacokinetics, and pharmacodynamics

24 weeks

Regular visits for dose-escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of spleen volume reduction and symptom score improvement

12 weeks

Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks thereafter during treatment

Long-term follow-up

Participants are monitored for overall survival and long-term safety outcomes

From start of treatment to end of study

What Are the Treatments Tested in This Trial?

Interventions

• TP-3654

Trial Overview The trial is testing TP-3654, an oral medication for myelofibrosis patients who are at intermediate or high risk. It's in early stages (Phase 1/2) to see how safe it is and how the body responds to different doses. Patients will also undergo regular bone marrow biopsies to monitor effects.

How Is the Trial Designed?

Group I: Arm 3: nuvisertib (TP-3654) in combination with momelotinib Experimental Treatment 2 Interventions

Group II: Arm 2: nuvisertib (TP-3654) added on to ruxolitinib Experimental Treatment 2 Interventions

Group III: Arm 1: nuvisertib (TP-3654) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Sumitomo Dainippon Pharma Oncology, Inc

Lead Sponsor

Trials

42

Recruited

6,800+

Sumitomo Pharma Oncology, Inc.

Lead Sponsor

Trials

45

Recruited

7,100+

Sumitomo Pharma America, Inc.

Lead Sponsor

Trials

244

Recruited

51,500+

Jatin Shah

Sumitomo Pharma America, Inc.

Chief Medical Officer since 2024

MD from an unspecified institution

Tsutomu Nakagawa

Sumitomo Pharma America, Inc.

Chief Executive Officer since 2024

MBA from Waseda University

Published Research Related to This Trial

Fedratinib, an oral JAK2 inhibitor, is effective and safe for treating myelofibrosis in patients with low platelet counts (50 to <100 × 10^9 /l), showing similar spleen and symptom response rates compared to patients with higher platelet counts in two clinical trials involving 193 patients.

While new or worsening thrombocytopaenia occurred more frequently in patients with low platelet counts (44% vs. 9% in high platelet counts), it was manageable with dose adjustments, and no serious thrombocytopaenia events were reported, indicating that initial dose adjustments for fedratinib are not necessary for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase-2 (JAK2), in patients with myelofibrosis and low pretreatment platelet counts. Harrison, CN., Schaap, N., Vannucchi, AM., et al.[2022]

In a pivotal phase III trial, fedratinib, an oral JAK2 inhibitor, demonstrated significant efficacy in treating myelofibrosis, with a 47% spleen volume response rate and a 40% symptom response rate at 24 weeks, compared to only 1% and 9% for placebo.

Fedratinib was generally well-tolerated, with common side effects including diarrhea, nausea, anemia, and vomiting, but notably, there were no cases of Wernicke encephalopathy reported in patients taking the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis. Pardanani, A., Tefferi, A., Masszi, T., et al.[2022]

In a study of 290 patients with myelofibrosis who discontinued ruxolitinib, half developed cytopenias, indicating a significant increase in morbidity after stopping the treatment.

The median overall survival after discontinuation was 11.1 months, with age, comorbidity index, and gender identified as key risk factors affecting treatment progression and survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient characteristics and outcomes after ruxolitinib discontinuation in patients with myelofibrosis. Mascarenhas, J., Mehra, M., He, J., et al.[2021]

Pacritinib has shown promising efficacy in treating myelofibrosis (MF), with 31% of patients experiencing a significant reduction in spleen volume and 42% showing improvement in spleen size through physical examination after 24 weeks.

The treatment demonstrated a favorable safety profile, particularly for patients with preexisting anemia and thrombocytopenia, although common side effects included diarrhea and nausea, leading to treatment discontinuation in 26% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Komrokji, RS., Seymour, JF., Roberts, AW., et al.[2022]

Ruxolitinib is an effective oral treatment for intermediate- or high-risk myelofibrosis, targeting JAK1 and JAK2 to reduce spleen size and improve symptoms, as demonstrated in Phase III trials with significant improvements in quality of life and overall survival.

The treatment has a manageable safety profile, with common side effects including anemia and thrombocytopenia, and requires dosage adjustments based on platelet counts, allowing for personalized patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of primary myelofibrosis. Swaim, SJ.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/655/530673/Nuvisertib-TP-3654-an-Investigational-Selective

Nuvisertib (TP-3654), an Investigational Selective PIM1 ... Preliminary data of TP-3654 in relapsed/refractory MF pts showed clinical activity including SVR25, symptom improvement correlating with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10431443/

P1031: PRELIMINARY DATA FROM THE PHASE 1/2 ... TP-3654, a highly selective PIM1 kinase inhibitor, showed spleen size reduction and bone marrow (BM) fibrosis reversion in JAK2V617F murine MF models.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04176198

NCT04176198 | A Study of Oral Nuvisertib (TP-3654) in ... This study is a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of nuvisertib ( ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124059317

Cytokine Modulation Correlates Strongly with Symptom ... The preliminary data of TP-3654 in relapsed/refractory MF pts showed promising clinical activity, including SVR, TSS improvement, and correlating cytokine ...

5. prnewswire.com prnewswire.com/news-releases/sumitomo-pharma-america-announces-that-nuvisertib-tp-3654-has-received-fda-fast-track-designation-for-the-treatment-of-myelofibrosis-302480390.html

Sumitomo Pharma America Announces that Nuvisertib (TP- ... Evaluable patients showed clinical activity including a ≥25% spleen volume reduction (SVR25) in 22.2% of patients and a ≥50% reduction in total ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6629/527865/A-Phase-1-2-Study-of-Nuvisertib-TP-3654-an

A Phase 1/2 Study of Nuvisertib (TP-3654), an Investigational ... Background: JAK inhibitors are the current standard of care treatment for patients (pts) with myelofibrosis (MF).

7. news.us.sumitomo-pharma.com news.us.sumitomo-pharma.com/2025-06-12-Sumitomo-Pharma-America-Announces-that-Nuvisertib-TP-3654-Has-Received-FDA-Fast-Track-Designation-for-the-Treatment-of-Myelofibrosis

Nuvisertib (TP-3654), an investigational highly selective ... The safety and efficacy of nuvisertib is currently being clinically evaluated in a Phase 1/2 study in patients with intermediate and high-risk ...

8. mpn-hub.com mpn-hub.com/medical-information/efficacy-and-safety-of-nuvisertib-in-mf-preliminary-phase-iii-data

Efficacy and safety of nuvisertib in MF: Preliminary phase I/ ... A 68-year-old male with primary myelofibrosis received ruxolitinib 10 mg twice daily for 7 months. His spleen size and symptoms are controlled, ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124094552

A Phase 1/2 Study of Nuvisertib (TP-3654), an ... Current monotherapy and preclinical data support the development of TP-3654 in combination with JAK inhibitors RUX or MMB in MF pts with low (<100 x 109/L) or ...